A unique case report of a revision extensor mechanism reconstruction using Marlex mesh in the setting of proximal tibial bone deficiency: The tantalum clamshell technique.

Extensor mechanism (EM) disruption is a rare but severe complication of total knee arthroplasty (TKA) that can greatly impair function. Treatment options for chronic patella tendon ruptures include primary repair, autograft augmentation, and reconstruction with allograft or synthetic material. Despite various techniques, failures can occur, and options for reconstruction after a failed allograft or mesh are limited, especially if the tibial component is well-fixed and cannot be easily removed, and if there is proximal tibial deficiency from a previous failed EM allograft. This case report presents a novel solution for revision EM reconstruction in a 72y.o. female patient with a history of multiple EM failures using an off-label Trabecular Metal Cone-Mesh-Cone (TM CMC) clamshell construct. The surgical procedure involved the removal of a non-viable allograft from the knee joint and the creation of a custom trabecular metal (TM) clamshell construct with a Marlex mesh graft in between the two TM implants. The customized TM cone was designed to cover the deficient anterior tibia and wrap around the ingrown TM cone. The Marlex mesh was cemented between the existing implant and the customized TM cone, and the construct was secured in place with two cancellous screws. The mesh was tunneled between soft tissue to prevent contact with the implant and rotated scar tissue was interposed to prevent abrasion of the mesh on the implant surfaces. The patient tolerated the procedure well and no complications were noted postoperatively. At a follow-up 12 months after the operation the patient remains satisfied with the result.

Osteoarthritis patients exhibit an autonomic dysfunction with indirect sympathetic dominance.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements. METHODS: Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed. RESULTS: GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level. CONCLUSIONS: This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.

Reconstruction of Chronic Quadriceps Tendon Rupture: The Quadriceps Advancement and Imbrication Technique.

BACKGROUND: Chronic extensor mechanism disruption after total knee arthroplasty (TKA) is a rare but challenging condition. There are several surgical approaches for quadriceps tendon repairs. In this report, we present a modified surgical technique for quadriceps tendon repair in chronic extensor mechanism disruption without the use of allografts or mesh augmentation. METHODS: We retrospectively reviewed 12 consecutive cases of chronic extensor mechanism with complete quadriceps tendon ruptures after TKA that underwent the advancement and imbrication technique. Patient outcomes were evaluated using the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, the range of motion and extensor lag measurements, and standardized lateral radiographs were reviewed for Insall-Salvati-Ratio preoperatively and at their most recent follow-up visit. RESULTS: There were 12 knees from patients who had a mean age of 72 years (range, 62 to 81) and were evaluated with a mean follow-up of 15.9 months (range, 11.4 to 50.9). The extensor lag significantly improved from 40.8 ± 31.9° (range, 10 to 90°) to 2.9 ± 6.9° (P = .014), the Insall-Salvati-Ratio significantly changed from 0.87 to 1.07 (P = .010), and the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement showed a significant difference: a raw score of 13.0 ± 5.8 versus 8.7 ± 5.6 (P = .002) and an interval score of 54.1 ± 14.0 versus 66.2 ± 15.6 (P = .001). CONCLUSIONS: Reconstruction of extensor mechanism in chronic quadriceps tendon ruptures after TKA with the advancement and imbrication technique showed excellent functional outcomes with no extensor lag and excellent restoration of motion. This technique can be combined with TKA revision surgery or used on its own. To ensure successful outcomes, the authors favor rigid immobilization for 12 weeks before starting mobilization.

Imaging in revision total knee arthroplasty: A novel 3D classification system for tibial bone defects.

PURPOSE: The primary purpose of the study was to use pre-revision total knee arthroplasty (TKA) computer-tomography (CT)-images to analyse typical tibial bone defects and create a new schematic three-dimensional (3D)-classification system. The secondary purpose was to investigate the association between defect size and implant selection at the time of revision surgery. METHODS: Eighty-four patients with preoperative CT-scans underwent revision of a primary TKA. CT-image segmentation with the 3D-Slicer Software was performed retrospectively, and a new three-dimensional classification system was used to grade tibial bone defects. The location of tibial bone defects was recorded for all cases. Volumetric 3D bone defect measurements were used to investigate the association between the bone defect volume, the indication for rTKA, and the use of modular revision components. The t-test, the Mann-Whitney-U test, and the Fisher's exact-test were used for group comparisons, and the Kruskal-Wallis test was used for multiple group comparisons. RESULTS: The most common anatomic regions for both contained and uncontained tibial bone defects were the anteromedial epiphysis (N = 50; mean epiphyseal-defect: 5.9 cm³) and metaphysis (N = 15; mean metaphyseal-defect: 9.6 cm³). A significant association was found between patients with preoperative metaphyseal defects (N = 22) and the use of tibial augments (N = 7) (p = 0.04). The use of cones/sleeves was associated with a significantly increased 3D-CT volume of the preoperative metaphyseal bone defects (p = 0.04). Patients with osteoporosis had significantly larger volumetric defects in the metaphysis (p = 0.01). CONCLUSION: Our results emphasise the importance of considering the three-dimensional nature of tibial defects in rTKA. The findings suggest that an understanding of the volume of the defect size through CT imaging can predict the need for augments and cones/sleeves and, especially in patients with osteoporosis can help the surgeon identify larger metaphyseal defects and ensure optimal metaphyseal fixation through appropriate implant selection. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Association Between Osteoarthritis Burden and Intervertebral Disk Degeneration in Patients Undergoing Lumbar Spine Surgery for Degenerative Lumbar Spondylolisthesis.

STUDY DESIGN: A retrospective analysis of prospectively collected data. OBJECTIVE: To assess the association between intervertebral disk degeneration and hip and knee osteoarthritis (OA) in patients with degenerative lumbar spondylolisthesis. BACKGROUND: The co-occurrence of hip OA and degenerative spinal pathologies was first described as the "hip-spine syndrome" and has also been observed in knee OA. It remains unclear whether both pathologies share an underlying connection beyond demographic factors. MATERIALS AND METHODS: Intervertebral disk degeneration was classified by the Pfirrmann Classification and intervertebral vacuum phenomenon. Intervertebral vacuum phenomenon was classified into mild (1 point), moderate (2 points), and severe (3 points) at each level and combined into a lumbar vacuum score (0-15 points). Similarly, a lumbar Pfirrmann grade was calculated (5-25 points). Patients with previous hip or knee replacement surgery were classified as having an OA burden. We used multivariable regression to assess the association between OA and disk degeneration, adjusted for age, body mass index, and sex. RESULTS: A total of 246 patients (58.9% female) were included in the final analysis. Of these, 22.3% had OA burden. The multivariable linear regression showed an independent association between OA burden and lumbar vacuum (ß = 2.1, P <0.001) and Pfirrmann grade (ß = 2.6, P <0.001). Representing a 2.1 points higher lumbar vacuum and 2.6 points higher lumbar Pfirrmann grade after accounting for demographic differences. CONCLUSIONS: Our study showed that OA burden was independently associated with the severity of the intervertebral disk degeneration of the lumbar spine. These findings give further weight to a shared pathology of OA of large joints and degenerative processes of the lumbar spine. LEVEL OF EVIDENCE: 3.

Validation of central peak height method for final adult height predictions on long leg radiographs.

Aims: Accurate skeletal age and final adult height prediction methods in paediatric orthopaedics are crucial for determining optimal timing of growth-guiding interventions and minimizing complications in treatments of various conditions. This study aimed to evaluate the accuracy of final adult height predictions using the central peak height (CPH) method with long leg X-rays and four different multiplier tables. Methods: This study included 31 patients who underwent temporary hemiepiphysiodesis for varus or valgus deformity of the leg between 2014 and 2020. The skeletal age at surgical intervention was evaluated using the CPH method with long leg radiographs. The true final adult height (FHTRUE) was determined when the growth plates were closed. The final height prediction accuracy of four different multiplier tables (1. Bayley and Pinneau; 2. Paley et al; 3. Sanders - Greulich and Pyle (SGP); and 4. Sanders - peak height velocity (PHV)) was then compared using either skeletal age or chronological age. Results: All final adult height predictions overestimated the FHTRUE, with the SGP multiplier table having the lowest overestimation and lowest absolute deviation when using both chronological age and skeletal age. There were no significant differences in final height prediction accuracy between using skeletal age and chronological age with PHV (p = 0.652) or SGP multiplier tables (p = 0.969). Adult height predictions with chronological age and SGP (r = 0.769; p ≤ 0.001), as well as chronological age and PHV (r = 0.822; p ≤ 0.001), showed higher correlations with FHTRUE than predictions with skeletal age and SGP (r = 0.657; p ≤ 0.001) or skeletal age and PHV (r = 0.707; p ≤ 0.001). Conclusion: There was no significant improvement in adult height prediction accuracy when using the CPH method compared to chronological age alone. The study concludes that there is no advantage in routinely using the CPH method for skeletal age determination over the simple use of chronological age. The findings highlight the need for more accurate methods to predict final adult height in contemporary patient populations.

Activity Following Total Hip Arthroplasty: Which Patients Are Active, and Is Being Active Safe?

BACKGROUND: Younger and physically active patients demand a return to sport after total hip arthroplasty (THA). However, because of the risk of implant wear and loosening, high-impact activities are often not recommended. The current study evaluates predictive factors and revision rates in patients with higher activity levels. METHODS: This retrospective study included 4152 hips in 3828 patients aged 45-75 that underwent primary THA for primary osteoarthritis between 2009 and 2019 with a minimum follow-up of 2 years. Pain and Lower Extremity Activity Scale (LEAS) were assessed before and 2 years after surgery. Activity was classified as low (LEAS 1-6), moderate (LEAS 7-13), or high (LEAS 14-18). RESULTS: Pain and LEAS improved from preoperative to 2-years postoperative (p < 0.001). The activity level was low in 6.2%, moderate in 52.9%, and high in 40.9% of the patients. Younger age, lower BMI, ASA, and CCI, male sex, and higher preoperative LEAS correlated with higher activity at 2 years (p < 0.001). The predicted revision-free survival rates between the activity groups were better for more highly active patients (p < 0.001). CONCLUSIONS: High physical activity 2 years following THA, with participating in sports like jogging several times a week, did not increase the risk of revision surgery. THA patients should not be prevented from a highly active lifestyle.

How safe are intra-articular corticosteroid injections to the hip?

BACKGROUND: Intra-articular corticosteroid injections (ICSI) are an effective symptomatic treatment for osteoarthritis of the hip. However, the safety of ICSI has been questioned and a relatively high risk for septic arthritis, rapidly progressive osteoarthritis (RPIO) and periprosthetic joint infections (PJI) in patients undergoing subsequent total hip arthroplasty (THA) have been suggested. METHODS: This is a retrospective evaluation of 682 hips that underwent ICSI with 40 mg of Triamcinolone for primary osteoarthritis of the hip. All ICSI were performed using sterile techniques, the number of ICSI in each hip and the cumulative corticosteroid dosage were assessed. Pre- and post-injection radiographs were compared to identify cases with RPIO. Native joint septic arthritis, surgical site infections and PJI were identified by chart review. RESULTS: 4 hips (0.6%) developed RPIO 2-4 months following ICSI. The cumulative Triamcinolone dose was not associated with the development of RPIO (p = 0.281). 1 case was diagnosed with septic arthritis and treated with staged THA, there were no signs of infection at a 5 years follow-up. 483 hips (75.7%) underwent THA, including 199 hips with THA less than 3 months following ICSI and 181 hips with > 1 ICSI prior to THA. There were 3 superficial surgical site infections/wound dehiscence and no PJI. CONCLUSION: The rate of RPIO was 0.6%. The current findings suggest that if ICSI is performed under sterile conditions, the risk for septic arthritis or PJI following THA, even in patients with multiple ICSI or ICSI within 3 months prior to surgery, is minimal.

Tibial bone defect prediction based on preoperative artefact-reduced CT imaging is superior to standard radiograph assessment.

PURPOSE: The purpose of this study was to evaluate the accuracy of preoperative CT-based Anderson Orthopaedic Research Institute (AORI)-grading and to correlate Computed tomography (CT)-based volumetric defect measurements with intraoperative AORI findings. METHODS: 99 patients undergoing revision total knee arthroplasty (rTKA) with preoperative CT-images were identified in an institutional revision registry. CT-image segmentation with 3D-Slicer Software was used to create 3D tibial bone defects which were then graded according to the AORI-classification. The AORI classification categorizes tibial defects into three types: Type I has healthy cortical and cancellous bone near the joint line, Type II involves metaphyseal bone loss affecting one or both condyles, and Type III indicates deficient metaphyseal bone with distal defects and potential damage to the patellar tendon and collateral ligament attachments. These 3D-CT gradings were compared to preoperative X-ray and intraoperative AORI grading. The Friedman test was used to investigate differences between AORI values of each measurement method. Volumetric 3D-bone defect measurements were used to investigate the relationship between AORI classification and volumetric defect size in the three anatomic zones of the tibia. RESULTS: Substantial agreements between preoperative 3D-CT AORI and intraoperative AORI (kappa = 0.663; P < 0.01) and fair agreements between preoperative X-ray AORI and intraoperative AORI grading (kappa = 0.304; P < 0.01) were found. Moderate correlations between volume of remaining bone and intraoperative AORI grading were found in epiphysis (rS = - 0.529; P < 0.001), metaphysis (rS = - 0.557; P < 0.001) and diaphysis (rS = - 0.421; P < 0.001). Small volumetric differences between AORI I vs. AORI II defects and relatively large differences between AORI II and AORI III defects in each zone were detected. CONCLUSION: Tibial bone defect prediction based on preoperative 3D-CT segmentation showed a substantial agreement with intraoperative findings and is superior to standard radiograph assessment. The relatively small difference in defect volume between AORI I, IIa and IIb suggests that updated CT-based classifications might hold benefits for the planning of rTKA. LEVEL OF EVIDENCE: Retrospective Cohort Study; III.

Patellar malalignment correlates with increased pain and increased synovial stress hormone levels-A cross-sectional study.

PURPOSE: Risk factors for the development of pain in the context of knee osteoarthritis (KOA) remain unclear. Radiological findings often do not correlate with clinical findings, so other pathomechanisms in the development and perception of pain must play a role. The purpose of this study is to investigate the correlation of increased sympathetic nervous system (SNS) activity (measured by subjective and objective chronic stress parameters) with KOA severity, patellofemoral malalignment, and pain. METHODS: 47 patients with KOA were assessed. Radiological measurements of tibiofemoral and patellofemoral parameters (Kellgren-Lawrence-score, patellar tilt (PT), Caton-Deschamps-Index and Hepp´s classification) were performed and correlated with knee-specific questionnaires (WOMAC®, KSS©) and chronic stress questionnaires (PSQ-20). Additionally, parameters associated with chronic stress were quantified in synovial fluid and serum samples from patients. RESULTS: PT correlated significantly with Caton-Deschamps-Index (r = 0.394,p = 0.006) and with medial patellofemoral joint space (r = 0.516,p<0.001). In addition, asymmetric trochlear groove (Hepp's classification > II) was associated with significantly higher PT values (p = 0.014). A negative correlation between PT and KSS©-symptoms subgroup was found (r = -0.340,p = 0.024). Patients with PT<5° had significantly higher scores in the Knee Society Score©-symptoms subgroup (p = 0.038). A positive and significant correlation between synovial aldosterone levels and PT was observed (r = 0.548,p = 0.042). CONCLUSION: The results of this study indicate that patellar malalignment might correlate with increased pain. The previous specification of standard PT values must be reconsidered as even low PT values seem to play a role in the occurrence of patellofemoral osteoarthritis symptoms. Lower PT values might lead to aggravated symptoms in patients with KOA due to a narrow medial patellofemoral joint space. In addition, PT might induce the release of synovial stress biomarkers and thus contribute to the progression of KOA.

[Spondylodiscitis]. / Spondylodiszitis.

Spondylodiscitis is a severe infectious disease of the spine that affects the intervertebral discs and adjacent vertebrae. It can lead to nonspecific pain, limited mobility, and destruction of spinal structures. Various pathogens, such as bacteria, fungi, or parasites, can trigger the disease. An early diagnosis and targeted treatment are crucial to reduce the risk of serious complications. Magnetic resonance imaging (MRI) with contrast agent and blood tests are essential for the diagnosis and assessing the course of the disease. The treatment includes conservative and surgical approaches. Conservative treatment consists of a minimum 6­week antibiotic course and immobilization of the affected area. Surgical interventions, along with several weeks of antibiotic therapy, are indicated for instabilities or complications in order to eliminate the infection focus and to restore spinal stability.

Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs.

Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.

Surgical Treatment of Spinal Deformities in Pediatric Orthopedic Patients.

Scoliosis and Scheuermann's disease are common spinal deformities that affect a substantial population, particularly adolescents, often impacting their quality of life. This comprehensive review aims to present a detailed understanding of these conditions, their diagnosis, and various treatment strategies. Through an extensive exploration of current literature, the review discusses the etiology of these spinal deformities and the use of diagnostic tools such as X-rays and MRI. It further delves into the range of treatment options available, from conservative approaches such as physiotherapy and bracing to more invasive surgical interventions. The review underscores the necessity of an individualized treatment approach, taking into account factors such as the patient's age, the severity of the curvature, and overall health. This all-encompassing perspective on scoliosis and Scheuermann's disease will aid in evidence-based decision making in their management with the goal of improving patient outcomes.

De Novo Synovial Chondromatosis following Primary Total Knee Arthroplasty: A Case Report.

In this case report, we present a rare case of a female patient who developed pain and swelling after a total knee arthroplasty. An extensive diagnostic workup including serum and synovial testing to rule out infection was performed in addition to advanced imaging including an MRI of the knee, but it was only after an arthroscopic synovectomy that the diagnosis of secondary synovial chondromatosis was confirmed. The purpose of this case report is to highlight the occurrence of secondary synovial chondromatosis as a rare cause of pain and swelling after total knee arthroplasty, thereby assisting clinicians in providing prompt diagnosis, surgical treatment, and efficient recovery in the setting of secondary synovial chondromatosis after total knee arthroplasty.

Factors for Prolonged Pain and Restriction of Movement Following Hemiepiphysiodesis Plating for the Correction of Lower Limb Malalignment in the Frontal Plane: An Explorative Analysis.

The correction of valgus leg malalignment in children using implant-mediated growth guidance is widely used and effective. Despite the minimal invasive character of the procedure, a relevant number of patients sustain prolonged pain and limited mobility after temporary hemiepiphysiodesis. Our aim was to investigate implant-associated risk factors (such as implant position and screw angulation), surgical- or anesthesia-related risk factors (such as type of anesthesia, use, and duration), and pressure of tourniquet or duration of surgery for these complications. Thirty-four skeletally immature patients with idiopathic valgus deformities undergoing hemiepiphysiodesis plating from October 2018-July 2022 were enrolled in this retrospective study. Participants were divided into groups with and without prolonged complications (persistent pain, limited mobility of the operated knee between five weeks and six months) after surgery. Twenty-two patients (65%) had no notable complications, while twelve patients (35%) had prolonged complications. Both groups differed significantly in plate position relative to physis (p = 0.049). In addition, both groups showed significant differences in the distribution of implant location (p = 0.016). Group 1 had a shorter duration of surgery than group 2 (32 min vs. 38 min, p = 0.032) and a lower tourniquet pressure (250 mmHg vs. 270 mmHg, p = 0.019). In conclusion, simultaneous plate implantation at the femur and tibia and metaphyseal plate positioning resulted in prolonged pain and a delay of function. In addition, the amplitude of tourniquet pressure or duration of surgery could play a factor.

Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro.

The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth factors or eicosanoids, indicate cancer-related inflammatory processes. Targeting these inflammatory mediators and related signal pathways may offer a rational strategy for the treatment of cancer. This study focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic dicarba-closo-dodecaboranes (carboranes) into dual cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. The di-tert-butylphenol derivative tebufelone represents a selective dual COX-2/5-LO inhibitor. The incorporation of meta- or para-carborane into the tebufelone scaffold resulted in eight carborane-based tebufelone analogs that show no COX inhibition but 5-LO inhibitory activity in vitro. Cell viability studies on HT29 colon adenocarcinoma cells revealed that the observed antiproliferative effect of the para-carborane analogs of tebufelone is enhanced by structural modifications that include chain elongation in combination with introduction of a methylene spacer resulting in higher anticancer activity compared to tebufelone. Hence, this strategy proved to be a promising approach to design potent 5-LO inhibitors with potential application as cytostatic agents.

Intra- and interobserver reliability analysis of pediatric lower limb parameters on digital long leg radiographs.

BACKGROUND: Malalignments of the lower extremity are common reasons for orthopedic consultation because it may lead to osteoarthritis in adulthood. An accurate and reliable radiological assessment of lower limb alignment in children and adolescents is essential for clinical decision-making on treatment of limb deformities and for regular control after a surgical intervention. OBJECTIVE: First, does the analysis of full-length standing anteroposterior radiographs show a good intra- and interobserver reliability? Second, which parameter is most susceptible to observer-dependent errors? Third, what is the Standard Error of Measurement (SEM95%) of the absolute femoral and tibial length? METHODS: Two observers evaluated digital radiographs of 144 legs from 36 children and adolescents with pathological valgus alignment before a temporary hemiepiphysiodesis and before implant removal. Parameters included Mechanical Femorotibial Angle (MFA), Mechanical Axis Deviation (MAD), mechanical Lateral Distal Femoral Angle (mLDFA), mechanical Medial Proximal Tibial Angle (mMPTA), mechanical Lateral Proximal Femoral Angle (mLPFA), mechanical Lateral Distal Tibial Angle (mLDTA), Joint Line Convergence Angle (JLCA), femur length, tibial length. Intra- and interobserver reliability (ICC2,1), SEM95% and proportional errors were calculated. RESULTS: The intra- and interobserver reliability for almost all measurements was found to be good to excellent (Intra-ICC2,1: 0.849-0.999; Inter-ICC2,1: 0.864-0.996). The SEM95% of both observers was found to be ± 1.39° (MFA), ± 3.31 mm (MAD), ± 1.06° (mLDFA) and ± 1.29° (mMPTA). The proportional error of MAD and MFA is comparable (47.29% vs. 46.33%). The relevant knee joint surface angles show a lower proportional error for mLDFA (42.40%) than for mMPTA (51.60%). JLCA has a proportional error of 138%. Furthermore, the SEM95% for the absolute values of the femoral and tibial length was 4.53 mm for the femur and 3.12 mm for the tibia. CONCLUSIONS: In conclusion, a precise malalignment measurement and the knowledge about SEM95% of the respective parameters are crucial for correct surgical or nonsurgical treatment. The susceptibility to error must be considered when interpreting malalignment analysis and must be considered when planning a surgical intervention. The results of the present study elucidate that MAD and MFA are equally susceptible to observer-dependent errors. This study shows good to excellent intra- and interobserver ICCs for all leg alignment parameters and joint surface angles, except for JLCA. TRIAL REGISTRATION: This study was registered with DRKS (German Clinical Trials Register) under the number DRKS00015053. LEVEL OF EVIDENCE: I, Diagnostic Study.

Correlation between Adrenoceptor Expression and Clinical Parameters in Degenerated Lumbar Intervertebral Discs.

Despite advanced knowledge of the cellular and biomechanical processes of intervertebral disc degeneration (IVDD), the trigger and underlying mechanisms remain unclear. Since the sympathetic nervous system (SNS) has been shown to exhibit catabolic effects in osteoarthritis pathogenesis, it is attractive to speculate that it also influences IVDD. Therefore, we explored the adrenoceptor (AR) expression profile in human IVDs and correlated it with clinical parameters of patients. IVD samples were collected from n = 43 patients undergoing lumbar spinal fusion surgery. AR gene expression was analyzed by semi-quantitative polymerase chain reaction. Clinical parameters as well as radiological Pfirrmann and Modic classification were collected and correlated with AR expression levels. In total human IVD homogenates α1A-, α1B-, α2A-, α2B-, α2C-, ß1- and ß2-AR genes were expressed. Expression of α1A- (r = 0.439), α2A- (r = 0.346) and ß2-AR (r = 0.409) showed a positive and significant correlation with Pfirrmann grade. α1A-AR expression was significantly decreased in IVD tissue of patients with adjacent segment disease (p = 0.041). The results of this study indicate that a relationship between IVDD and AR expression exists. Thus, the SNS and its neurotransmitters might play a role in IVDD pathogenesis. The knowledge of differential AR expression in different etiologies could contribute to the development of new therapeutic approaches for IVDD.

Clinical outcomes in patients receiving edoxaban or phenprocoumon for prevention of stroke in atrial fibrillation: a German real-world cohort study.

BACKGROUND: Appropriate and timely anticoagulant therapy with vitamin K antagonists (VKAs) or non-vitamin K oral antagonists (NOACs) is essential for stroke prevention in non-valvular atrial fibrillation (NVAF). Comparative data regarding effectiveness and safety for edoxaban vs phenprocoumon, the predominant VKA in Germany, are scarce. OBJECTIVES: The study evaluates effectiveness and safety of edoxaban vs phenprocoumon in NVAF patients in a German real-world setting. METHODS: German statutory health insurance claims data of the Institute for Applied Health Research Berlin (InGef) Research Database from 2014 until 2019 were analyzed. In NVAF patients, new users of edoxaban and phenprocoumon were compared to assess effectiveness (stroke/systemic embolism (SE)) and safety (bleeding) during therapy. Hazard ratios (HR) were estimated through multiple outcome-specific cox proportional hazard models adjusting for baseline characteristics. Outcomes of geriatric patients were analyzed in subgroup analyses. RESULTS: Between 2015 and 2018, 7,975 and 13,319 NVAF patients newly initiated treatment with edoxaban or phenprocoumon. After adjusting for baseline confounders, the risk of stroke/SE (HR: 0.85, 95% CI: 0.70-1.02) was numerically but not significantly lower, while the risk of major bleeding (HR: 0.69, 95% CI: 0.58-0.81) was significantly lower for edoxaban. In the geriatric subgroups, homogenous results compared to the main analysis were obtained. CONCLUSION: The results of this real-world analysis indicated better effectiveness and safety outcomes in patients with NVAF initiating edoxaban treatment compared to phenprocoumon. The findings confirm that the beneficial effects observed in the pivotal ENGAGE AF-TMI 48 trial can also be achieved in real-world use of edoxaban.

Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay.

Matrix metalloproteinases (MMPs) play crucial roles in tissue homeostasis and pathologies by remodeling the extracellular matrix. Previous studies have demonstrated the biological activities of MMP-derived cleavage products. Furthermore, specific fragments can serve as biomarkers. Therefore, an in vitro cleavage assay to identify substrates and characterize cleavage patterns could provide important insight in disease-relevant mechanisms and the identification of novel biomarkers. In the pathogenesis of osteoarthritis (OA), MMP-2, -8, -9 and -13 are of vital importance. However, it is unclear which protease can cleave which matrix component. To address this question, we established an in vitro cleavage assay using recombinantly expressed MMPs and the two cartilage matrix components, COMP and thrombospondin-4. We found a time- and concentration-dependent degradation and an MMP-specific cleavage pattern for both proteins. Cleavage products can now be enriched and purified to investigate their biological activity. To verify the in vivo relevance, we compared the in vitro cleavage patterns with serum and synovial fluid from OA patients and could indeed detect fragments of similar size in the human samples. The cleavage assay can be adapted to other MMPs and substrates, making it a valuable tool for many research fields.